Major Research Findings

Pemigatinib, a selective FGFR inhibitor, has shown promising results in the treatment of advanced unresectable cholangiocarcinoma with FGFR2 fusions or rearrangements. 5 . It has been approved by the FDA for this indication. 5 . However, the clinical utility of FGFR inhibitors may be limited by resistance mechanisms and side effect profile. 5 . A better understanding of the unique toxicities related to FGFR inhibitors can help us prevent and effectively manage FGFR-inhibitor-induced adverse events, thereby enhancing their clinical benefit. 5 .

Reasons for Side Effects

Side effects of FGFR inhibitors are potentially related to the inhibition of FGFR signaling and the critical role of FGFR in cell proliferation and differentiation. 5 .

Common Side Effects

Nail Abnormalities

Pemigatinib treatment can cause nail disorders, such as onycholysis, discoloration, and thickening. 1 4 .

Hyperphosphatemia

Hyperphosphatemia is a common side effect of pemigatinib treatment. 1 3 . It can lead to tumoral calcinosis, which is characterized by soft tissue calcifications. 3 .

Taste Disturbances

Taste disorders are another reported side effect of pemigatinib. 1 .

Palmar-plantar Erythrodysesthesia Syndrome

Pemigatinib can cause palmar-plantar erythrodysesthesia syndrome. 4 .

Stomatitis

Stomatitis is a possible side effect of pemigatinib treatment. 4 .

Calciphylaxis

Calciphylaxis is a rare but possible side effect of pemigatinib treatment. 4 .

Side Effect Management

Nail Abnormalities

Nail abnormalities can be managed by discontinuing pemigatinib, nail care, and the use of moisturizers. 4 .

Hyperphosphatemia

Hyperphosphatemia can be managed by a phosphorus-restricted diet, phosphate binders, and dialysis. 4 .

Taste Disturbances

Taste disturbances can be managed by dietary changes, the use of taste enhancers, and consultation with a taste specialist. 4 .

Palmar-plantar Erythrodysesthesia Syndrome

Palmar-plantar erythrodysesthesia syndrome can be managed by the use of moisturizers, cold compresses, and steroid creams. 4 .

Stomatitis

Stomatitis can be managed by the use of mouthwashes, analgesics, and steroid creams. 4 .

Calciphylaxis

Calciphylaxis can be managed by calcium supplementation, vasodilators, and immunosuppressants. 4 .

Comparison Among Studies

Similarities

The studies all highlight the effectiveness of FGFR inhibitors in treating cholangiocarcinoma with FGFR2 fusion or rearrangement. 5 6 2 . They also emphasize that FGFR inhibitors can cause adverse effects. 4 1 3 .

Differences

There are some differences in the effectiveness, side effects, and usage of FGFR inhibitors discussed in these studies. 5 6 2 4 1 3 . For instance, one study suggests pemigatinib is more effective than infigratinib. 2 . Another study shows that pemigatinib can lead to side effects like nail abnormalities and hyperphosphatemia. 1 3 .

Considerations for Real-Life Applications

While FGFR inhibitors hold promise for treating cholangiocarcinoma with FGFR2 fusion or rearrangement, it is crucial to remember that these drugs can have side effects. 5 4 . Patients should have a detailed discussion with their doctors about the benefits and risks of these medications before starting treatment. 5 .

Limitations of Current Research

The limited sample size and narrow participant groups in these studies necessitate further research. 5 6 2 . Additionally, as these studies primarily focus on pemigatinib's effectiveness and safety, more research is needed to evaluate the efficacy and safety of other FGFR inhibitors. 5 .

Future Research Directions

Future research should delve deeper into the effectiveness and safety of FGFR inhibitors. 5 . This entails conducting larger clinical trials, exploring other FGFR inhibitors, and developing novel approaches to prevent or manage side effects related to FGFR inhibitors. 5 .

Conclusion

FGFR inhibitors represent a promising new treatment option for cholangiocarcinoma with FGFR2 fusion or rearrangement. 5 . These medications can potentially shrink tumors and extend patient survival. 5 . However, FGFR inhibitors can have side effects. Before starting treatment, patients should engage in a thorough discussion with their doctors about the benefits and risks of these medications. 5 .